HIV Clinical Updates: New Single-Tablet Regimens

Sebaaly, Jamielynn; Kelley, Denise

doi:10.1177/1060028018793252

Cited by 11 publications

(6 citation statements)

References 73 publications

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“…Regimens can become complex when there is need to take multiple pills, requirements to take a medication fasted or with food, or potential for interactions with other medications, including those required to treat HIV-related comorbidities ( 3 , 7 , 8 ). New treatment options that are not only highly effective but also offer excellent tolerability, a high barrier to resistance, favorable drug interaction profiles, and the potential for less frequent dosing remain the focus of much clinical research ( 7 , 9 ). While 1 pill once a day meets the needs of many PLWH, for others, daily administration poses challenges, including treatment fatigue and daily reminders and/or stigma associated with ART ( 10 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and Safety Profile of the Novel HIV Nonnucleoside Reverse Transcriptase Inhibitor MK-8507 in Adults without HIV

Ankrom

Rudd

Schaeffer

et al. 2021

Antimicrob Agents Chemother

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MK-8507 is a novel HIV-1 non-nucleoside reverse transcriptase inhibitor in clinical development with potential for once-weekly oral administration for the treatment of HIV-1 infection. Two randomized, double-blind, placebo-controlled phase 1 studies in adults without HIV-1 evaluated the safety, tolerability, and pharmacokinetics of single and multiple doses of MK-8507; drug interaction with midazolam (a cytochrome P450 3A4 substrate) and food effect were also assessed. In Study 1, 16 participants received oral ascending single doses of MK-8507 (2–400 mg) or placebo in an alternating fashion. In Study 2, 24 participants received ascending single doses of MK-8507 (400–1200 mg) or placebo and multiple doses (once weekly for 3 weeks) of MK-8507 (100–400 mg) or placebo. MK-8507 pharmacokinetics were approximately dose proportional at 2–1200 mg. MK-8507 had a time to maximum concentration of 2–7 hours and a mean terminal half-life of ∼58–84 hours. MK-8507 doses ≥100 mg achieved a plasma concentration at 168 hours post-dose (7 days) associated with antiviral efficacy. A high-fat meal had no clinically meaningful effect on MK-8507 pharmacokinetics, and MK-8507 400 mg once weekly had no clinically meaningful effect on midazolam pharmacokinetics. Single and multiple doses of MK-8507 were generally well tolerated. No trends with dose and no clinically meaningful changes were observed in vital signs, electrocardiograms, and laboratory safety tests. The pharmacokinetics and safety data are supportive of once-weekly oral administration and support further clinical investigation of MK-8507 for the treatment of HIV-1 infection. Over the last 3 decades, substantial improvements have been made in oral HIV antiretroviral therapies (ART), which now offer people living with HIV (PLWH) the potential for a near-normal life expectancy (1, 2). To achieve this, individuals must maintain life-long viral suppression, which requires daily administration of efficacious medication (3). Issues surrounding tolerability, complicated regimens, and treatment fatigue from daily dosing can lead to poor adherence and suboptimal viral suppression (3–6). Regimens can become complex when there is the need to take multiple pills, requirement to take a medication fasted or with food, or the potential for interactions with other medications, including those required to treat HIV-related comorbidities (3, 78). New treatment options that are not only highly effective but also offer excellent tolerability, a high barrier to resistance, favorable drug interaction profiles, and the potential for less frequent dosing remain the focus of much clinical research (7, 9). While 1 pill once a day meets the needs of many PLWH, for others daily administration poses challenges, including treatment fatigue and daily reminders and/or stigma associated with ART (10, 11). While treatment regimens that can be taken less often than daily are attractive to many PLWH, the long-acting injectable combination of cabotegravir/rilpivirine is currently the only treatment option available without daily dosing; however, administration requires injection by a health care professional (12), potentially posing other challenges.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and Safety Profile of the Novel HIV Nonnucleoside Reverse Transcriptase Inhibitor MK-8507 in Adults without HIV

Ankrom

Rudd

Schaeffer

et al. 2021

Antimicrob Agents Chemother

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“…Although contemporary ART has enabled many patients with HIV infection to live with durable viral suppression using a convenient once-daily single-tablet regimen, treatment-experienced patients with MDR HIV infection often struggle to achieve and maintain viral suppression with currently available ARVs. [32][33][34] IBA, a new agent with a distinct mechanism of action and nonoverlapping patterns of resistance, represents an option to construct ARV regimens that may effectively and durably suppress viral replication and restore and maintain immune function in this difficult-totreat patient population. 14,15 The DHHS guidelines for the use of ARVs in adults with HIV recommend the initiation of new regimens with at least 2 fully active agents for patients who fail to achieve undetectable viral load because of resistance.…”

Section: Relevance To Patient Care and Clinical Practicementioning

confidence: 99%

Ibalizumab: The First Monoclonal Antibody for the Treatment of HIV-1 Infection

Chahine

Durham

2020

Ann Pharmacother

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Objective: To review the efficacy and safety of ibalizumab (IBA) in the treatment of HIV-1 infection. Data Sources: A literature search was performed using PubMed and Google Scholar (2010 to mid-June 2020) with the search terms TMB-355, TNX-355, and ibalizumab. Other resources included abstracts presented at recent conferences and the manufacturer’s website and prescribing information. Study Selection and Data Extraction: All relevant English-language articles of studies assessing the efficacy and safety of IBA were included. Data Synthesis: IBA is a monoclonal antibody that blocks HIV-1 from infecting CD4+ T cells. IBA is approved by the Food and Drug Administration, in combination with other antiretrovirals (ARVs), for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant (MDR) HIV-1 infection failing their current ARVs. IBA demonstrated significant and sustained antiviral activity in patients with MDR HIV-1 infection who had advanced disease and limited treatment options. It carries a warning regarding the development of immune reconstitution inflammatory syndrome. Common adverse reactions include diarrhea, dizziness, nausea, and rash. Relevance to Patient Care and Clinical Practice: IBA represents an attractive option for treatment-experienced adults with advanced HIV-1 infection who are no longer able to achieve viral suppression on oral ARV therapy alone and who are able to adhere to an infusion therapy every 2 weeks. As with other biologics, there is a potential for the development of antibodies to IBA that can compromise its efficacy and safety. Conclusion: IBA provides a needed treatment option to achieve and maintain viral suppression in heavily treatment-experienced adults with MDR HIV-1 infection.

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“…The era of STRs began in 2006 with the marketing authorisation of efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) combination. Since then, ten more STRs have been developed and marketed [2] . The recognised advantages of a single pill administered daily include simplification, reduced pill burden, improved quality of life and increased adherence to therapy, resulting in a higher number of patients with undetectable vi-ral load, decreased hospitalisation rates and increased retention in care compared with multiple-tablet regimens [ 1 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of pre‐existent drug resistance on virological efficacy of single‐tablet regimens in people living with HIV

Stella

Volpicelli

Carlo

et al. 2022

International Journal of Antimicrobial Agents

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HIV Clinical Updates: New Single-Tablet Regimens

Abstract: STRs and agents in the pipeline continue to simplify ART regimens, increase medication adherence, and minimize toxicities.

Cited by 11 publications

References 73 publications

Pharmacokinetic and Safety Profile of the Novel HIV Nonnucleoside Reverse Transcriptase Inhibitor MK-8507 in Adults without HIV

Pharmacokinetic and Safety Profile of the Novel HIV Nonnucleoside Reverse Transcriptase Inhibitor MK-8507 in Adults without HIV

Ibalizumab: The First Monoclonal Antibody for the Treatment of HIV-1 Infection

Impact of pre‐existent drug resistance on virological efficacy of single‐tablet regimens in people living with HIV

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